The term "progestational" means "preceding gestation" and some known progestational agents stimulate a condition of pseudopregnancy. Thus these agents are useful as contraceptives and in the treatment of disorders associated with menstrual irregularities. Most known progestational agents are not produced by the human body but yet function in a manner similar to natural gestagens (e.g. progesterone). Thus much research time and resources have been devoted to developing progestational compounds having high potency (i.e., which may accordingly be administered in small amounts and yet be effective) and relatively low, if any, side effects. Progestational activity is generally determined by the so-called Clauberg assay wherein a compound whose activity is to be evaluated is administered to estrogen-primed female rabbits and glandular development of the uterine endometrium is scored on a 0 to +4 basis according to the McPhail scale (Kirk-Othmer, Encyclopedia of Chemical Technology, 3rd Edition, Volume 12, Wiley-Interscience).
Perhaps the best known gestagen is progesterone, a naturally occurring hormone formed in the adrenals, ovaries, and placenta and which is the major female sex hormone required for the maintenance of pregnancy. Progesterone is a 21-carbon steroid secreted by the corpus luteum and which has the following structure wherein the numbering system and alphabetic ring designation system conventionally used when naming derivatives not having well known trivial names is shown: ##STR4## where, as will be the convention throughout the specification and claims, substituents attached to the ring system from above are designated .beta. and represented by a solid line while substituents attached from below are designated .alpha. and represented by a dashed line.
Synthetic progesterone is readily available (e.g., from the Upjohn Company, Kalamazoo, Mich.). Progesterone is only weakly active when taken orally, however, and has been replaced almost entirely by more active oral gestagens.
Molecular biologists and endocrinologists have now established the principal features of the molecular mechanisms involved in steroid hormone action (see Receptors and Hormone Action, Ed. B. W. O'Malley and L. Birnbaumer, Vols. I and II, Academic Press, N.Y., 1978). For hormonal action to occur the steroid hormone must enter the endocrine-responsive cell. Endocrine-responsive cells are characterized by possessing, both in the cytoplasm and in the nucleus, a specific protein with high binding affinity for the steroid hormone known as the "hormone receptor protein" or simply as "receptor protein". Such receptor proteins are characterized by their high specificity for the steroid and by their capacity to distinguish through their binding affinities very small structural differences between steroids.